Metabolomics study of treatment response to conbercept of patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

Yinchen Shen; Hanying Wang; Xiaoyin Xu; Chong Chen; Shaopin Zhu; Lu Cheng; Junwei Fang; Kun Liu; Xun Xu

doi:10.3389/fphar.2022.991879

Metabolomics study of treatment response to conbercept of patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

Front Pharmacol. 2022 Sep 19:13:991879. doi: 10.3389/fphar.2022.991879. eCollection 2022.

Authors

Yinchen Shen^{1

2

3

4

5}, Hanying Wang^{1

2

3

4

5}, Xiaoyin Xu^{1

2

3

4

5}, Chong Chen^{1

2

3

4

5}, Shaopin Zhu^{1

2

3

4

5}, Lu Cheng^{1

2

3

4

5}, Junwei Fang^{1

2

3

4

5}, Kun Liu^{1

2

3

4

5}, Xun Xu^{1

2

3

4

5}

Affiliations

¹ Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² National Clinical Research Center for Eye Diseases, Shanghai, China.
³ Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.
⁴ Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
⁵ Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.

Abstract

Background: Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are major causes of blindness in aged people. 30% of the patients show unsatisfactory response to anti-vascular endothelial growth factor (anti-VEGF) drugs. This study aims to investigate the relationship between serum metabolome and treatment response to anti-VEGF therapy. Methods: A prospective longitudinal study was conducted between March 2017 and April 2019 in 13 clinical sites in China. The discovery group were enrolled from Shanghai General Hospital. The validation group consisted of patients from the other 12 sites. Participants received at least one intravitreal injection of 0.5 mg anti-VEGF drug, conbercept, and were divided into two groups - responders and non-responders. Serum samples of both groups were processed for UHPLC-MS/MS analysis. We constructed principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models to investigate the metabolic differences between two groups using SIMCA-P. Area under curve (AUC) was calculated to screen the biomarkers to predict treatment response. Metabolites sub-classes and enriched pathways were obtained using MetaboAnalyst5.0. Results: 219 eyes from 219 patients (nAMD = 126; PCV = 93) were enrolled. A total of 248 metabolites were detected. PCA and PLS-DA models of the discovery group demonstrated that the metabolic profiles of responders and non-responders clearly differed. Eighty-five differential metabolites were identified, including sub-classes of diacylglycerophosphocholines, lysophosphatidylcholine (LPC), fatty acids, phosphocholine, etc. Responders and non-responders differed most significantly in metabolism of LPC (p = 7.16 × 10^-19) and diacylglycerophosphocholine (p = 6.96 × 10^-17). LPC 18:0 exhibited the highest AUC, which is 0.896 with 95% confidence internal between 0.833 and 0.949, to discriminate responders. The predictive accuracy of LPC 18:0 was 72.4% in the validation group. Conclusions: This study suggests that differential metabolites may be useful for guiding treatment options for nAMD and PCV. Metabolism of LPC and diacylglycerophosphocholine were found to affect response to conbercept treatment. LPC 18:0 was a potential biomarker to discriminate responders from non-responders.

Keywords: anti-vegf; metabolomics; neovascular age-related macular degeneration; polypoidal choroidal vasculopathy; treatment response.